AB0387 THE RELATIONSHIP BETWEEN JAK INHIBITORS AND CREATINE KINASE ELEVATION IN PATIENTS WITH RHEUMATOID ARTHRITIS: A REAL-WORLD CLINICAL STUDY
Authors: M. Tada, T. Okano, K. Mamoto, Y. Yamada, K. Orita, K. Mandai, S. Anno, T. Iida, K. Inui, T. Koike
Journal: Annals of the Rheumatic Diseases (2022)

Background Some cases of creatine kinase (CK) elevation caused by Janus kinase (JAK) inhibitor treatment for rheumatoid arthritis (RA) have been reported in clinical trials 1 . However, the frequency and patients’ background characteristics in clinical practice are unknown. Objectives The correlation between JAK inhibitor treatment for RA and changes in CK levels in clinical practice were investigated using a multicenter database. Methods The multicenter database of JAK inhibitors was used, and 103 (tofacitinib 46, baricitinib 44, upadacitinib 11, peficitinib 1, filgotinib 1) of 265 RA patients were followed up at 24 weeks, and their CK levels were evaluated. The time-dependent change of CK was evaluated by sex and analyzed by the Wilcoxon signed-rank test. The percentage abnormal from the standard titer was calculated. The factors related to an elevated CK at 24 weeks were investigated using patients’ background characteristics at the time of starting JAK inhibitors by univariate analysis. Results Women accounted for 85.4% of the patients, the median age was 68 years, disease duration was 15 years, and the mean DAS28ESR was 5.00. The CK levels of both men and women were significantly elevated at 4 weeks and maintained until 24 weeks (men, women: 63, 62 (0 weeks), 101, 95 (4 weeks), 119, 96 (12 weeks), 155, 99 (24 weeks), U/L, P&lt;0.001) (Figure 1). The percentage abnormal was also significantly increased at 4 weeks and maintained until 24 weeks (5.8% (0 weeks), 20.7% (4 weeks), 26.3% (12 weeks), 24.3% (24 weeks), P=0.002). The factors significantly positively related to elevated CK levels at 24 weeks were male, CK, creatinine, and lactate dehydrogenase (LDH), and stage, class, modified health assessment questionnaire, estimated glomerular filtration rate (eGFR), and glucocorticoid use were significantly negatively correlated (Table 1). There were no significant differences in CK elevation among the agents. Table 1. Characteristics at the time of starting JAK inhibitors related to elevated creatine kinase levels at 24 weeks Univariate Data at stating JAK inhibitors R value P value Creatine kinase 0.653 &lt;0.001 Gender, men 0.247 0.012 Steinbrocker stage -0.215 0.039 Steinbrocker class -0.277 0.008 modified health assessment questionnaire -0.268 0.008 Creatinine 0.289 0.003 eGFR -0.231 0.019 LDH 0.201 0.041 Glucocorticoid use -0.409 0.008 Analyzed by Spearman rank correlation coefficient Figure 1. Time-dependent changes of CK in all RA patients Conclusion CK was significantly elevated at 4 weeks and maintained until 24 weeks. However, no patients complained of muscle pain and stopped JAK inhibitors. Patients with high CK, low eGFR, high LDH, or maintained activities of daily living at the time of starting JAK inhibitors tended to have high CK levels at 24 weeks. References [1]Fleischmann, R. et al. Upadacitinib Versus Placebo or Adalimumab in Patients With Rheumatoid Arthritis and an Inadequate Response to Methotrexate: Results of a Phase III, Double-Blind, Randomized Controlled Trial. Arthritis &amp; rheumatology (Hoboken, N.J. ) 71, 1788-1800, doi:10.1002/art.41032 (2019). Disclosure of Interests None declared